Dose Ranging Trial of Tipranavir/Ritonavir in Treatment-Experienced HIV Infected Individuals

HIV Infections Clinical Trial

Official title:

Double-Blind, Randomized, Dose Optimization Trial of Three Doses of Tipranavir Boosted With Low Dose Ritonavir (TPV/RTV) in Multiple Antiretroviral Drug-Experienced Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00034866
• Other study ID #: BI 1182.52
• Status: Completed
• Phase: Phase 2
• First received: May 2, 2002
• Last updated: September 19, 2005
• Start date: April 2002
• Est. completion date: October 2002

Study information

• Verified date: September 2005
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to determine which of three different dose combinations of tipranavir and ritonavir, when taken with a standard approved anti-HIV drug therapy, is most effective and safe. Tipranavir is an investigational protease inhibitor which has been demonstrated to have in vitro activity against HIV-1.

Description:

This study will be conducted in HIV+, multiple ARV medication experienced patients. All patients must have received treatment from each of three ARV classes: NRTIs, NNRTIs and PIs, have received at least two PI-based ARV regimens (may include the current regimen) with a viral load greater than or equal to 1000 copies/mL at the time of study entry. The two separate PI-based regimens must each have been taken for at least 3 months. At least one resistance-conferring PI-mutation (from a pre-established panel) must be present. Baseline genotypic screening will be performed and will be used in conjunction with ARV medication history to determine new background therapy for each individual subject to use.

Following genotypic screening at baseline, qualifying subjects will be randomized to one of three blinded treatment regimens. Subjects will discontinue their current protease inhibitor and initiate TPV/RTV for 2 weeks of functional monotherapy. Thereafter, the background ARV medications will be optimized and subjects will remain on blinded TPV/RTV plus optimized background therapy for the duration of the trial. Trial duration ranges between 12-32 weeks, depending on when the subject is entered into the trial and the interim analyses for determination of optimized TPV/RTV regimen is completed. On determination of the optimal TPV/RTV dose, subjects may opt to continue open-label treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: October 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent prior to trial participation.

2. HIV-1 infected males or females >= 18 years of age.

3. At least 3 months experience taking NRTIs, NNRTI(s), and PIs.

4. Current PI-based ARV medication regimen for at least 3 months prior to randomization, and at least 3 months experience taking at least one other PI-based regimen.

5. HIV-1 viral load >= 1000 copies/mL at screening.

6. Genotypic resistance report indicating one or more primary PI resistance mutation(s), including 30N, 46I/L, 48V, 50V, 82A/F/T, 84V or 90M, with not more than one of 82 A/F/T or 84V or 90M.

7. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if severity is no higher than Grade 3 GGT, Grade 2 cholesterol or triglycerides, and no higher than Grade 1 for all other tests based on the DAIDS Grading Scale. All laboratory values outside these limits are subject to approval by BI.

8. Acceptable medical history, as assessed by the investigator, with chest X-ray and ECG within 1 year of study participation.

9. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system, such as: grapefruit or Seville oranges or their products; herbal preparations containing St. John’s Wort or milk thistle, and garlic supplements.

10. A prior AIDS defining event is acceptable as long as it has resolved or the subject has been on stable treatment for at least 2 months.

Exclusion Criteria:

1. ARV medication naïve.

2. Female subjects who:

• have a positive serum pregnancy test at screening or during the study

• are breast feeding

• are planning to become pregnant

• are not willing to use two barrier methods of contraception (e.g. latex condom plus spermicidal jelly/foam).

3. Any active opportunistic infection within 60 days before study entry.

4. Active Hepatitis B or C disease defined as HBsAg positive or HCV RNA positive with AST/ALT >Grade 1.

5. Prior tipranavir use.

6. Use of investigational medications within 30 days before study entry or during the trial. Some expanded access drugs may be acceptable; must be approved by BI. Tenofovir, investigational at time of preparation of this protocol, is acceptable.

7. Use of concomitant drugs which may significantly reduce plasma levels of the study medications.

8. Use of immunomodulatory drugs (e.g. interferon, cyclosporin, hydroxyurea, interleukin-2).

9. Active substance abuse.

10. Inability to swallow TPV or RTV capsules.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Protease inhibitor tipranavir

Locations

Country	Name	City	State
Puerto Rico	Clinical Research Puerto Rico	San Juan
United States	Albany Medical College	Albany	New York
United States	(IDC) Research Institute	Altamonte Springs	Florida
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Infectious Disease Physicians Research	Annandale	Virginia
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	John's Hopkins University School of Medicine	Baltimore	Maryland
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	CORE Center, Cook County Hospital	Chicago	Illinois
United States	Rush Presbyterian/St. Luke's Medical Center	Chicago	Illinois
United States	Burnside Clinic	Columbia	South Carolina
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Nelson-Tebedo Clinic	Dallas	Texas
United States	Atlanta VA Medical Center, Dept. of ID	Decatur	Georgia
United States	Henry Ford Hospital, Infectious Diseases Dept.	Detroit	Michigan
United States	Duke University Medical Center Infectious Diseases Clinic	Durham	North Carolina
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Orange County Center for Special Immunology	Fountain Valley	California
United States	ID Care, Inc.	Hillsborough	New Jersey
United States	Gathe Clinic	Houston	Texas
United States	Jemsek Clinic	Huntersville	North Carolina
United States	Kansas City Free Health Clinic	Kansas City	Missouri
United States	Wellness Center	Las Vegas	Nevada
United States	Living Hope Clinical Trials Inc.	Long Beach	California
United States	AHF Research Center	Los Angeles	California
United States	ID Care, Inc.	Los Angeles	California
United States	Tower I.D. Medical Assoc., Inc.	Los Angeles	California
United States	University of California, Los Angeles Medical Center	Los Angeles	California
United States	University of So. California / LA County USC Medical Center	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Mercer University School of Medicine	Macon	Georgia
United States	Jackson Medical Tower	Miami	Florida
United States	Vanderbilt University - AIDS Clinical Trial Unit	Nashville	Tennessee
United States	HIV Outpatient Program (H.O.P.)	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	Infect. Disease Institute, Clinical Trials Unit	Oklahoma City	Oklahoma
United States	Phoenix Body Positive	Phoenix	Arizona
United States	ID Care, Inc.	Randolph	New Jersey
United States	Pacific Horizon Medial Group	San Francisco	California
United States	University of California San Francisco Positive Health Program Research	San Francisco	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Steinhart Medical Associates	South Miami	Florida
United States	CRI Community Research Initiative	Springfield	Massachusetts
United States	Washington University AIDS Clinical Trial Unit	St. Louis	Missouri
United States	University of New York at Stony Brook	Stony Brook	New York
United States	Hillsborough County Health Dept.	Tampa	Florida
United States	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida
United States	Dupont Circle Physicians Group	Washington	District of Columbia
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest University Baptist Medical Center	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Puerto Rico,